The major goal during the past year has been to evaluate the response of the pancreatic B-cell to resistance to insulin-mediated glucose disposal-the basic defect in patients with non-insulin dependent diabetes mellitus. Results to date have shown that: 1) the sensitivity of the B-cell to increases in plasma glucose concentration is enhanced in insulin resistant individuals; and 2) the net effects of this change in sensitivity is an enhanced secretion of both insulin and proinsulin.